The anti-inflammatory activities of
kakkalide, a major constituent of the flower of Pueraria thunbergiana, and
irisolidone, a metabolite of
kakkalide produced by intestinal microflora, against
carrageenan-induced
inflammation in air pouches on the backs of mice and in
lipopolysaccharide (LPS)-stimulated peritoneal macrophages were investigated.
Kakkalide and
irisolidone down-regulated the gene expression of
cytokines [
tumor necrosis factor alpha (TNF-α) and
interleukin-1 beta (IL-1β)] and
cyclooxygenase-2 (COX-2) and the production of pro-inflammatory
cytokines, TNF-α and IL-1β, and inflammatory mediators, NO and
prostaglandin E(2) (
PGE(2)), in LPS-stimulated peritoneal macrophages. These agents also inhibited the phosphorylation of IκB-α and the nuclear translocation of
nuclear factor-kappa B (NF-κB). Orally administered
kakkalide and
irisolidone significantly reduced
carrageenan-induced inflammatory markers, leukocyte number, and
protein amount in the exudates of the air pouch. These constituents also inhibited
PGE(2) production and COX-2
inducible nitric oxide synthase, IL-1β, and TNF-α expression. These agents also inhibited NF-κB activation. The anti-inflammatory effects of
irisolidone were more potent than those of
kakkalide. Based on these findings,
kakkalide and
irisolidone may inhibit inflammatory reactions via NF-κB pathway, and
irisolidone, a metabolite of
kakkalide, may more potently inhibit these inflammatory reactions.